The catabolisms of deoxy-ATP and ATP were compared in cultured human T lymphoblastoid cells incubated under various conditions. It was found that in the presence of deoxycoformycin, an inhibitor of adenosine deaminase, deoxyadenosine was the only product of deoxy-ATP catabolism. In contrast, the main products of ATP catabolism in either the presence or the absence of deoxycoformycin were inosine and hypoxanthine. These results demonstrate that deoxy-ATP catabolism proceeds exclusively via deoxyadenosine deamination, whereas ATP catabolism proceeds mainly via adenylate deamination. These findings thus provide an explanation for the selective deoxynucleotide metabolic abnormalities associated with adenosine deaminase deficiency in humans.